Metabolic readouts of tumor instructed normal tissues (TINT) identify aggressive prostate cancer subgroups for tailored therapy.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-04-07 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1426949

Ilona Dudka, João Figueira, Pernilla Wikström, Anders Bergh, Gerhard Gröbner

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引用次数: 0

Abstract

Introduction: Prostate cancer (PC) diagnosis relies on histopathological examination of prostate biopsies, which is restricted by insufficient sampling of all tumors present. Including samples from non-PC but tumor instructed normal tissues (TINT) may increase the diagnostic power by displaying the adaptive responses in benign tissues near tumors.

Methods: Here, we applied high-resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) to identify metabolomic biomarkers of possible diagnostic value in benign prostate tissues near low/high-grade tumors.

Results: Benign samples near high-grade tumors (B ISUP 3 + 4) exhibited altered metabolic profiles compared to those close to low-grade tumors (B ISUP 1 + 2). The levels of six metabolites differentiated between the two groups; myo-inositol, lysine, serine and combined signal of lysine/leucine/arginine were increased in benign samples near high-grade tumors (B ISUP 3 + 4) compared to near low-grade tumors (B ISUP 1 + 2), while levels of ethanolamine and lactate were decreased. Additionally, we revealed metabolic differences in non-cancer tissues as a function of their distance to the nearest tumor. Eight metabolites (glutathione, glutamate, combined signal of glutamate/glutamine - glx, glycerol, inosine, ethanolamine, serine and arginine) differentiated between benign tissue located close to the tumor (d ≤ 5 mm) compared to those far away (d ≥ 1 cm).

Conclusion: Our HR MAS NMR-based approach identified metabolic signatures in prostate biopsies that reflect the response of benign tissues to the presence of nearby located tumors in the same prostate and confirmed the power of the TINT concept for improved PC diagnostics and understanding of tumor-tissue interactions.

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肿瘤指示正常组织（TINT）的代谢读数识别侵袭性前列腺癌亚群，以进行定制治疗。

简介：前列腺癌（PC）的诊断依赖于前列腺活检的组织病理学检查，这受到所有肿瘤样本不足的限制。包括来自非pc但肿瘤指示的正常组织（TINT）的样本可以通过显示肿瘤附近良性组织的适应性反应来提高诊断能力。方法：在这里，我们应用高分辨率魔角旋转核磁共振（HR MAS NMR）来鉴定低/高级别肿瘤附近良性前列腺组织中可能具有诊断价值的代谢组学生物标志物。结果：高级别肿瘤附近的良性样本（B ISUP 3 + 4）与低级别肿瘤附近的良性样本（B ISUP 1 + 2）相比，代谢谱发生了改变。两组间6种代谢物水平存在差异；良性肿瘤附近（B ISUP 3 + 4）的肌醇、赖氨酸、丝氨酸和赖氨酸/亮氨酸/精氨酸联合信号较低级别肿瘤附近（B ISUP 1 + 2）升高，而乙醇胺和乳酸水平降低。此外，我们还揭示了非癌组织的代谢差异与最近肿瘤的距离有关。8种代谢物（谷胱甘肽、谷氨酸、谷氨酸/谷氨酰胺- glx联合信号、甘油、肌苷、乙醇胺、丝氨酸和精氨酸）在肿瘤附近（d≤5 mm）和远处（d≥1 cm）良性组织之间有差异。结论：我们基于HR MAS核磁共振的方法确定了前列腺活检中的代谢特征，这些特征反映了良性组织对同一前列腺附近肿瘤的反应，并证实了TINT概念在改进PC诊断和理解肿瘤与组织相互作用方面的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.